The present invention relates to a method for the determination of the concentration of lithium ions in an aqueous medium. More particularly, the invention relates to an electrochemical method of high sensitivity and reliability for the determination of the concentration of lithium ions in an aqueous medium which also contains ions of other alkali metals and alkaline earth metals even when the concentration of lithium ions is very low.
As is known, lithium compounds are widely used, among many other important applications, as a therapeutic medicament for psychopathic patients suffering depression. It is important in the therapeutic treatment of a patient of depression by administration of a lithium containing medicament that the concentration of lithium ions in the blood is maintained at an effective level, for example, in the range from 0.5 to 1.0 mM. When the concentration of lithium ions in blood is too low, the therapeutic effect obtained thereby is of course insufficient. When the concentration of lithium ions in blood is too high, for example, in the range from 2.0 to 2.5 mM, on the other hand, various side effects are caused. Therefore, it is essential to periodically monitor the lithium ion concentration in the patient's blood and it is eagerly desired in the psychopathology to develop an accurate, rapid and convenient method for the determination of lithium ions in blood.
No practical method or apparatus, which meets the above mentioned requirements, however, is known mainly because blood always contains ions of alkali metals other than lithium, i.e., sodium and potassium, and alkaline earth metals, e.g., typically, calcium, in concentrations much higher than the lithium ion concentration to interfere detection and determination of lithium ions.
Several electrochemical methods have been proposed by using a sensor membrane electrode containing a neutral lithium ionophore. Examples of such an ionophore include crown ethers such as 14 crown-4-derivatives and 15-crown-4-derivatives disclosed in Journal of the American Chemical Society, Volume 106 (1984), page 6978, amide ethers disclosed in Analytical Chemistry, volume 58 (1986), page 1948, polypropoxylate adducts disclosed in Analyst, Volume 110 (1985), page 1381 and the like. A comprehensive review is given for lithium ion selective electrodes in ion-Selective Electrode Review, Volume 8 (1986), page 173. Sensors, e.g., electrodes, using these lithium ionophores are influenced by sodium ions badly affecting the accuracy of the concentration determination of lithium ions in blood.